. 2022 Sep 1;148(9):811-818.

doi: 10.1001/jamaoto.2022.1743.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis

Mirabelle Sajisevi¹, Lisa Caulley^{2

3

4}, Antoine Eskander^{5

6}, Yue Jennifer Du⁷, Edel Auh⁸, Alexander Karabachev⁹, Peter Callas¹⁰, Wilhelmina Conradie^{11

12}, Lindi Martin¹³, Jesse Pasternak¹⁴, Bahar Golbon¹⁴, Lars Rolighed¹⁵, Amr H Abdelhamid Ahmed¹⁶, Arvind Badhey¹⁷, Anthony Y Cheung¹⁶, Martin Corsten¹⁸, David Forner¹⁸, Jeffrey C Liu^{19

20}, Dorsa Mavedatnia²¹, Charles Meltzer²², Julia E Noel²³, Vishaal Patel¹⁹, Arun Sharma²⁴, Alice L Tang⁹, Gabriel Tsao²⁵, Mandakini Venkatramani²⁶, Michelle Williams²⁷, Sean M Wrenn²⁶, Mark Zafereo²⁸, Brendan C Stack Jr²⁴, Gregory W Randolph^{16

29}, Louise Davies^{30

31

32}

Affiliations

¹ Department of Surgery, Division of Otolaryngology, University of Vermont Medical Center, Burlington.
² Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Canada.
³ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁵ Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Sunnybrook Health Sciences Centre and Michael Garron Hospital, Toronto, Ontario, Canada.
⁶ Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada.
⁷ Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Ontario, Canada.
⁸ Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
⁹ Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
¹⁰ Larner College of Medicine, University of Vermont, Burlington.
¹¹ Division of Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
¹² Breast and Endocrine Unit, Tygerberg Hospital, Cape Town, South Africa.
¹³ Division of Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁴ Department of Surgery, University of Toronto, Ontario, Canada.
¹⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark.
¹⁶ Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts.
¹⁷ Department of Otolaryngology, University of Massachusetts, Worcester.
¹⁸ Division of Otolaryngology-Head & Neck Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁹ Department of Otolaryngology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
²⁰ Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
²¹ Faculty of Medicine, University of Ottawa, Ontario, Canada.
²² The Permanente Medical Group, Santa Rosa, California.
²³ Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Stanford, California.
²⁴ Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
²⁵ The Permanente Medical Group, Fremont, California.
²⁶ Department of Surgery, Rush University Medical Center, Chicago, Illinois.
²⁷ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston.
²⁸ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston.
²⁹ Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston.
³⁰ Veterans Affairs Outcomes Group, White River Junction, Vermont.
³¹ Section of Otolaryngology-Head & Neck Surgery, The Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
³² Associate Editor, JAMA Otolaryngology-Head & Neck Surgery.

PMID: 35834240
PMCID: PMC9284406
DOI: 10.1001/jamaoto.2022.1743

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis

Mirabelle Sajisevi et al. JAMA Otolaryngol Head Neck Surg. 2022.

. 2022 Sep 1;148(9):811-818.

doi: 10.1001/jamaoto.2022.1743.

Authors

Affiliations

¹ Department of Surgery, Division of Otolaryngology, University of Vermont Medical Center, Burlington.
² Department of Otolaryngology-Head and Neck Surgery, University of Ottawa, Canada.
³ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
⁵ Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Sunnybrook Health Sciences Centre and Michael Garron Hospital, Toronto, Ontario, Canada.
⁶ Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada.
⁷ Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Ontario, Canada.
⁸ Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
⁹ Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
¹⁰ Larner College of Medicine, University of Vermont, Burlington.
¹¹ Division of Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
¹² Breast and Endocrine Unit, Tygerberg Hospital, Cape Town, South Africa.
¹³ Division of Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁴ Department of Surgery, University of Toronto, Ontario, Canada.
¹⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark.
¹⁶ Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, Massachusetts.
¹⁷ Department of Otolaryngology, University of Massachusetts, Worcester.
¹⁸ Division of Otolaryngology-Head & Neck Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁹ Department of Otolaryngology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
²⁰ Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
²¹ Faculty of Medicine, University of Ottawa, Ontario, Canada.
²² The Permanente Medical Group, Santa Rosa, California.
²³ Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Stanford University, Stanford, California.
²⁴ Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.
²⁵ The Permanente Medical Group, Fremont, California.
²⁶ Department of Surgery, Rush University Medical Center, Chicago, Illinois.
²⁷ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston.
²⁸ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston.
²⁹ Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston.
³⁰ Veterans Affairs Outcomes Group, White River Junction, Vermont.
³¹ Section of Otolaryngology-Head & Neck Surgery, The Dartmouth Institute for Health Policy & Clinical Practice, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
³² Associate Editor, JAMA Otolaryngology-Head & Neck Surgery.

PMID: 35834240
PMCID: PMC9284406
DOI: 10.1001/jamaoto.2022.1743

Abstract

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease.

Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location.

Design, setting, and participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade.

Main outcomes and measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022.

Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries.

Conclusions and relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Caulley reported grants from the Canadian Institutes of Health Research (Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award) and from PSI (Research Trainee Award) outside the submitted work. Dr Williams reported scientific advisory and speaking fees from Bayer outside the submitted work. Dr Zafereo reported research grants from Merck and Eli Lilly outside the submitted work. Dr Randolph reported grants from Eisai outside the submitted work and holding the position of president of the International Thyroid Oncology Group and the World Congress on Thyroid Cancer, chairperson of the Administrative Division of the American Head and Neck Society and governor of the American College of Surgeons−Otolaryngology Governor. No other disclosures were reported.

Figures

**Figure 1.. Modes of Detection Classification Algorithm With Case Examples**
Abbreviations: CT, computed tomography; MEN, multiple endocrine neoplasia; MRI, magnetic resonance imaging; PCP, primary care practitioner; PET, positron emission tomography; US, ultrasonography.

**Figure 2.. Distribution of Thyroid Cancer Diagnosis, by Trigger Event**
Abbreviation: MOD, mode of detection.

See this image and copyright information in PMC

Comment in

Most Thyroid Surgeries Start With an Asymptomatic Patient.
Drake T, Caicedo-Granados E. Drake T, et al. JAMA Otolaryngol Head Neck Surg. 2022 Sep 1;148(9):818-819. doi: 10.1001/jamaoto.2022.1744. JAMA Otolaryngol Head Neck Surg. 2022. PMID: 35834231 No abstract available.
Asymptomatic Patients and Rising Incidence of Thyroid Cancer.
Yang S, Xu X. Yang S, et al. JAMA Otolaryngol Head Neck Surg. 2022 Dec 1;148(12):1185-1186. doi: 10.1001/jamaoto.2022.3367. JAMA Otolaryngol Head Neck Surg. 2022. PMID: 36301561 No abstract available.
Asymptomatic Patients and Rising Incidence of Thyroid Cancer-Reply.
Sajisevi M, Davies L. Sajisevi M, et al. JAMA Otolaryngol Head Neck Surg. 2022 Dec 1;148(12):1186. doi: 10.1001/jamaoto.2022.3370. JAMA Otolaryngol Head Neck Surg. 2022. PMID: 36301567 No abstract available.

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Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis

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Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis

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